Little is known about the pathogenesis of tubulointerstitial nephritis, scarring and progressive renal damage, that is, reflux nephropathy, caused by vesicoureteral reflux. While vesicoureteral reflux may be associated with symptomatic infections, it may also be clinically silent and may cause progressive nephropathy without infection in children. Reflux in the absence of infection has also been shown to cause progressive nephropathy in rats, and pigs. Since fully formed urine has been shown to gain retrograde access to the lymphatic and venous circulations in both vesicoureteral reflux in childhood as well as in experimental vesicoureteral reflux, one possible mechanism of renal damage may be an autoimmune response to some urinary constituent. Tamm-Horsfall protein, a major normally occurring mammalian urinary protein which is synthesized only in renal tubular epithelial cells, has received recent attention as a potential antigen because of the detection of circulating antibodies to Tamm-Horsfall protein in adults with urinary tract obstruction and infection, in school-age girls with symptomatic upper urinary tract infection and in pigs with vesicoureteral reflux. The purpose of this proposal therefore, is to define the immunopathogenic role of Tamm-Horsfall Protein (THP), a normal urinary glycoprotein, in the production of reflux nephropathy. Methods have been developed and others are proposed to measure the immunologic responses to THP in (l) an experimental rabbit model of tubulointerstitial nephritis (2) a pig model of reflux nephropathy (3) children with vesicoureteral reflux and (4) adults with obstructive uropathies.